tbuckley/cabot-search huggingface dataset:
Thrombocytopenic myelofibrosis (MF) patients previously treated with a JAK inhibitor in a phase 3 randomized study of momelotinib (MMB) versus danazol (DAN) [MOMENTUM].
Authors: Aaron Thomas Gerds, Srdan Verstovsek, Alessandro Vannucchi, Haifa Kathrin Al-Ali, David Lavie, Andrew T. Kuykendall, Sebastian Grosicki, Alessandra Iurlo, Yeow Tee Goh, Mihaela Cornelia Lazaroiu, Miklos Egyed, Maria Laura Fox, Donal P. McLornan, Andrew Perkins, Sung-Soo Yoon, Vikas Gupta, Jean-Jacques Kiladjian, Rafe Donahue, Jun Kawashima, Ruben A. Mesa
Journal: Journal of Clinical Oncology (2022)

7061 Background: MMB, an oral JAK1/2 and ACVR1/ALK2 inhibitor, showed clinical activity on MF symptoms, RBC transfusion requirements (anemia), and spleen volume in the SIMPLIFY trials, including in MF patients (pts) with thrombocytopenia. MOMENTUM is a pivotal phase 3 study of symptomatic and anemic MF pts previously treated with a JAK inhibitor (JAKi) testing MMB vs DAN. This analysis evaluated MOMENTUM pts with baseline (BL) platelet counts (PLT) ≤150 x 10 9 /L. Methods: Eligibility: Primary or post-ET/PV MF; DIPSS high risk, Int-2, or Int-1; MF Symptom Assessment Form Total Symptom Score (MFSAF TSS) ≥10; Hgb &lt;10 g/dL; prior JAKi for ≥90 days, or ≥28 days if RBC transfusions ≥4 units in 8 weeks (wks) or Gr 3/4 thrombocytopenia, anemia, or hematoma; palpable spleen ≥5 cm; PLT ≥25 x 10 9 /L. JAKi taper and washout was ≥21 days. Randomization: 2:1 to MMB 200 mg QD plus DAN placebo or DAN 600 mg QD plus MMB placebo for 24 wks. Primary endpoint: TSS response (≥50% reduction from BL) rate at wk 24. Key secondary endpoints, assessed sequentially at wk 24: RBC transfusion independence (TI) rate, splenic response rate (SRR; ≥25% reduction in volume from BL), change from BL in TSS, SRR (≥35% reduction from BL) and rate of zero transfusions since BL. Results: 60 (74%) of 81 MMB pts and 25 (58%) of 43 DAN pts with BL PLT ≤150 x 10 9 /L completed the 24-week randomized treatment (RT) phase. Median BL TSS were 29 (MMB) and 24 (DAN), Hgb were 7.9 (MMB) and 8.0 (DAN) g/dL, and PLT were 67 x 10 9 /L (MMB) and 64 x 10 9 /L (DAN). Prior JAKi was ruxolitinib in 124 pts (100%) and fedratinib in 6 pts (5%). Efficacy results are in Table. These results are consistent with the overall ITT analysis set (N=195). Most common Gr ≥3 TEAEs in the RT phase were thrombocytopenia (MMB, 31%; DAN, 16%) and anemia (MMB, 7%; DAN, 14%); Gr ≥3 bleeding events occurred in 9% of MMB and 5% of DAN pts. TEAEs led to study drug discontinuation in 15% of MMB and 19% of DAN pts in RT phase. A trend toward improved OS up to wk 24 was seen with MMB vs DAN [HR (95% CI)=0.490 (0.195, 1.235)]. Additional analyses of pts with BL PLT &lt;100 x 10 9 /L (N=100) and BL PLT &lt;50 x 10 9 /L (N=31) show similar treatment effects of MMB vs DAN. Conclusions: In thrombocytopenic MF pts who were symptomatic and anemic, MMB was superior to DAN for symptom responses, transfusion requirements, and spleen responses and showed comparable safety and favorable survival. MMB may address a critical unmet need in thrombocytopenic MF pts. Clinical trial information: NCT04173494. [Table: see text]
Efficacy and safety of second-line (2L) therapy in patients with relapsed small cell lung cancer (SCLC): A systematic literature review (SLR).
Authors: Abhishek A. Nair, Christina S. Kwon, Sharada Harricharan, Xinke Zhang
Journal: Journal of Clinical Oncology (2022)

e20576 Background: Although SCLC is sensitive to first-line chemotherapy, most patients experience relapse, and options for 2L therapy are limited. Patients with relapsed SCLC have a poor prognosis, particularly those with resistant disease. To better understand the clinical unmet need of relapsed SCLC, we conducted a SLR of the efficacy and safety of currently approved 2L treatments for SCLC. Methods: EMBASE, MEDLINE, Cochrane databases (01/1990-11/2021), and congress abstracts (2020-21) were queried in accordance with the Preferred Reporting Item for Systematic Reviews and Meta-Analyses (PRISMA) guidelines using Population, Intervention &amp; Comparators, Outcomes and Study Design (PICOS) criteria to identify interventional studies involving 2L SCLC treatments. Efficacy and safety data were extracted in overall populations (O), as well as platinum-sensitive (S) and resistant (R) subgroups. Efficacy data including overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and duration of response (DoR) were summarized for currently approved treatments including topotecan (T), amrubicin (A), and lurbinectedin (L) monotherapies. Results: Of the 4,329 records identified, 130 studies were selected, of which 35 studies investigated T (22 studies), A (15 studies) and L (1 study) monotherapies (3 studies comparing A vs T) and outcomes by these treatments are presented (Table). Median OS ranged from 5.0 to 12.0 months in O, 3.4 to 11.0 in R, and 5.0 to 14.4 months in S. Median PFS was up to 4 months in O and R. ORR ranged widely by treatments. Median DoR was 3.1 to 5.3 months in O, less than 5 months in R, and 10 months in S. Among studies reporting overall safety, grade 3+ adverse events (AEs) were observed in 72%-96% and 74%-93% of patients with T (n = 308 from 3 studies) and A (n = 526 from 3 studies), respectively. The most common grade 3+ AEs in patients with L (n = 105) were neutropenia (46%) followed by leucopenia (29%). Conclusions: Relapsed SCLC patients treated with currently approved treatments have poor survival outcomes, especially those with resistant disease. A significant unmet need exists for treatment options extending survival and durability.[Table: see text]
LGG-58. Understanding the transcriptional heterogeneity of pediatric low-grade gliomas and its implication for tumor pathophysiology
Authors: Michelle Boisvert, Ashwyn A Perera, Alexandra L Condurat, John Jeang, Jessica W Tsai, Dana Novikov, Kevin Zhou, Madison Chacon, Jeromy DiGiacomo, Rushil Kumbhani, Dayle Wang, Michael D Taylor, Jordan R Hansford, Louise Ludlow, Nada Jabado, Keith L Ligon, Rameen Beroukhim, Pratiti Bandopadhayay, David T W Jones
Journal: Neuro-Oncology (2022)

Abstract Pediatric low-grade gliomas (pLGGs) are the most frequent brain tumors in children and comprise a heterogeneous group of tumors with different locations, histologic subtypes, ages at presentation, and clinical behavior. Tumors frequently respond to treatment with chemotherapy or surgical removal, but they can regrow after a period of quiescence, requiring further therapy. Thus, a deeper understanding of the molecular processes involved in these tumors is required to develop therapeutic strategies that are effective against their disease mechanisms. To better understand the cellular behaviors of this heterogenous group of tumors, we have employed single-cell and single-nuclei RNA sequencing technologies to analyze a large-scale dataset (&amp;gt;250,000 cells) of pLGGs. Analysis of this data identified a heterogenous population of cell types and cell states, detecting mature and progenitor-like astrocytes and oligodendrocytes, as well as cells exhibiting senescence or cycling programs. Moreover, we identify a significant immune infiltrate, comprised primarily of microglia. In addition to heterogeneity within pLGG tumors, heterogeneity between LGG subtypes represents another layer that stratifies pLGG biology. We performed a compositional analysis of the cell types present in these tumors and compared transcription signatures and gene expression programs across shared cellular populations of histologically and genetically distinct pLGGs. Finally, we optimized our integration and batch correction analyses by using external 293T cells as spike in controls during our single-cell and single-nuclei data generation steps to determine the most suitable method for batch-effect removal. Our analysis of human pLGGs at the single-cell and single-nuclei resolution provides critical insight into the heterogenous biological activities that constitute these tumors.
Efficacy of a nurse monitoring service at preventing disease- or therapy-related symptoms in patients receiving targeted therapy or immunotherapy.
Authors: Andrea Sbrana, Andrea Antonuzzo, Carla Ida Ripamonti, Fausto Roila, Daniele Santini, Alessandra Fabi, Paola Ermacora, Gianmauro Numico, Raffaele Barbara, Deborah Coletta, Laura Velutti, Domenico C. Corsi, Alfredo Berruti, Gabriella Mariani, Paolo Bossi
Journal: Journal of Clinical Oncology (2022)

12118 Background: The safety profile of Targeted therapies (TT) and immunotherapy (IT) may be underestimated and negatively affect the clinical outcome. Methods: A nationwide, randomized, open-label trial (NCT04726020) conducted among 29 Italian centers involved two cohorts of 223 adult patients (pts) with a solid tumor, receiving TT (group B, 119 pts) or IT (group C, 104 pts). Pts were randomized to receive a weekly nurse monitoring phone call, together with an educational leaflet with some practical advice about toxicities (experimental arm), or only the educational leaflet (control arm). In the experimental arm, pts received their monitoring phone call before their treatment began, then every week for up to 16 weeks of treatment were completed. The primary objective was the evaluation of the difference in toxicities according to patient-reported outcome (PRO)-CTCAE. Results: Both arms were comparable in terms of pts’ characteristics (e.g. site of primary tumor, line of treatment). The adherence to the project (that is the completion of every expected call) was 62.1% in group B and 66.9% in group C. In group B, in the experimental arm, we found a higher number of pts without pain (53.7 vs 39.9%, p = 0.047); a trend of lower fatigue (29.2 vs 18%, p = 0.067) was also observed. In group C, a higher number of pts did not report fatigue (29.1 vs 17.5%, p = 0.043), shortness of breath (61.4 vs 38.5%, p = 0.002) or dry skin (72 vs 52.3%, p = 0.004). More pts also referred to be without pain (51.6 vs 38.8%, p = 0.065) and pruritus (75.9 vs 64.5%, p = 0.088), even if these difference were not statistically significant. Conclusions: The use of PRO assessment through active nurse monitoring might lead to a better tolerance of TT and IT with possible implications on pts’ quality of life and ultimately on treatment outcome. In particular, in the IT group, several symptoms were prevented from occurring, thus encouraging a major effort to implement such active monitoring in this population. Clinical trial information: NCT04726020.
Functional and oncological outcomes of female pelvic organ preserving robot-assisted radical cystectomy
Authors: E. Lavallee, Z. Dovey, P. Pathak, L. Day, L. Renström Koskela, A. Hosseini, N. Waingankar, R. Mehrazin, J. Sfakianos, A. Hosseini, P. Wiklund
Journal: European Urology (2022)
Auto-reactive antibodies as predictive markers for immune checkpoint–induced pneumonitis.
Authors: Mehmet Altan, Qi Wang, Quan-Zhen Li, Chengsong Zhu, Hai T. Tran, Ajay Sheshadri, Saumil Gandhi, Mara Antonoff, Stephen Swisher, Natalie I Vokes, Amy R. Spelman, J. Jack Lee, Jianjun Zhang, John Heymach
Journal: Journal of Clinical Oncology (2022)

2554 Background: Certain immune-related adverse events (irAEs) that emerge with immune checkpoint blockade share clinical features of autoimmune conditions. Preexisting auto-reactive antibodies and their contribution to irAEs have not been well defined, and observations are limited. Methods: We longitudinally collected patient plasma samples from a clinical trial that combines immune checkpoint inhibitors, Ipilimumab, and Nivolumab (I+N) with subsequent radiation therapy (Lonestar, NCT03391869). Plasma samples were collected at baseline, after 12 weeks of I+N (induction), and at the time of Grade ≥ 2 pneumonitis (CTCAEv5.0). Auto reactive antibody profiles were analyzed using a fluorescence-based assay system that measures more than 130 antigens and is capable of assaying antibody reactivity for IgG and IgM fractions, including nuclear-cytosolic and tissue-specific antigens. Selected antibodies had a reportable result range, reference intervals, and reproducibility with quality controls. A paired t-test was used to compare the mean of longitudinally collected baseline and toxicity samples. An unpaired t-test was used to compare differences between groups. The False Discovery Rate was used to control the Type I error rate of multiple comparisons. Results: In the study cohort, G≥2 pneumonitis was observed in 11 patients out of 194 (5.6%). Serum was collected at baseline for all 11 patients, and 9 of the 11 patients had a serum sample collected at the time of pneumonitis event. Longitudinal serum samples (baseline and post-induction) collected from 32 patients without any irAEs were used as control. At baseline AChR3 and calmodulin antibodies were elevated in patients who developed pneumonitis, compared with baseline samples from controls (p≤0.05). At the time of pneumonitis IgM antibodies against AChR3, CXCL10, NSE, BAFF, CA242, Cytokeratin 19 were noted to be elevated in serum for pneumonitis cases compared with post induction samples from control (p≤0.005). Conclusions: We identified auto reactive antibodies associated with a higher risk of immunotherapy associated pneumonitis in patients treated with ipilimumab and nivolumab. These included auto reactive antibodies against proteins associated with lung injury (AChR3), lung inflammation (BAFF, CXCL10) and against alveolar epithelium (Cytokeratin 19). Future studies are warranted to determine if auto-reactive antibodies can be used as pre-treatment risk markers or to diagnose pneumonitis and may offer insights into to mechanisms that predispose toward pneumonitis.
Survival outcomes in patients with metastatic breast cancer treated with eribulin: A real-world evidence study from India.
Authors: Ashok K. Vaid, Jyoti Wadhwa, Nagender Sharma, Devender Sharma, Ashok Sen, Dheeraj Gautam
Journal: Journal of Clinical Oncology (2022)

e13053 Background: Eribulin is a novel synthetic analogue of halichondrin B, which acts as a microtubule inhibitor by interacting with the microtubules and inhibits the G2-M growth phase. Eribulin was approved for metastatic breast cancer (MBC) based on landmark EMBRACE (phase-3) trial, although only a small number of Asian subgroups of the population were included, and data in the Indian subset of patients is limited. Therefore, in this real-world study we retrospectively assessed the clinical outcomes of eribulin in Indian women with metastatic breast cancer (heavily pre-treated). Methods: Adult MBC patients who had advanced following at least two chemotherapy lines, including anthracyclines and taxanes, in either an adjuvant or metastatic setting and were treated with eribulin over several lines were retrospectively analyzed. Records pertaining to socio-demographics, clinical, pathology, imaging, and therapy were reviewed. The overall survival (OS), progression-free survival (PFS), and tumor response were calculated. Results: A total of 80 patients were included. The median age of patients was 54.5 years (range: 27-82). Eribulin was majorly used as a second-line and third-line chemotherapy agent in 28 (35 percent) and 24 (30 percent) of MBC patients, respectively. In 57 evaluable patients, the best objective response rate (ORR) was 43.85 percent, while the clinical benefit rate was 59.65 percent with eribulin therapy. The median OS and PFS were 17.29 (95 percent CI: 14.31-20.27) and 11.76 (95 percent CI: 9.5-14.02) months, respectively. There was positive correlation between the number of cycles and the outcomes of survival, with patients getting more than 6 cycles having superior OS and PFS. On subgroup analysis, patients with liver metastasis had significantly (p&lt;0.001) lower mean OS (9.42 months) and PFS (3.69 months) than other sites. Conclusions: This real-world retrospective study supports and confirms the efficacy of eribulin in Indian patients with MBC (heavily pre-treated). It should be considered in the strategy of several chemotherapy lines in MBC.
Nivolumab with ipilimumab for MSI-H colorectal cancer with liver metastases.
Authors: Vasiliki Michalaki, Theodosios Theodosopoulos, George Frangoulidis, Nikolaos Dafnios, Ioannis Papakonstantinou, Antonios Vezakis, Christos Papadimitriou
Journal: Journal of Clinical Oncology (2022)

e15556 Background: Immune checkpoint inhibitor (ICI) therapy has recently demonstrated durable clinical benefit in patients with advanced mismatch repair deficient (dMMR) colorectal cancer. The aim of this study was to test the combination of nivolumab and ipilimumab in microsatellite instability-high (MSI-H) colorectal cancer patients with oligometastatic liver disease. Methods: Twelve patients with MSI-H mCRC and one prior line of treatment for metastatic disease received nivolumab 3 mg/kg plus ipilimumab 1 mg/kg once every 3 weeks (four doses) followed by nivolumab 3 mg/kg once every 2 weeks until disease progression or discontinuation. The primary endpoint was objective response rate (ORR). Results: At baseline, the patients’ median age was 58 years (range, 51-67 years), and 40.7 % of patients were women. Sites of metastases included liver (89.8%), distant lymph nodes (43.6%), and lungs (9.2%). For all 12 patients (median follow-up was 8.2 months), ORR was 71% (95% CI 46.3–78.6). Of 12 patients enrolled, 4 patients (33%) achieved a partial response, and 5 patients (41%) achieved stable disease. Responses were consistent with the overall population across subgroups including age, Eastern Cooperative Oncology Group (ECOG) performance status, prior adjuvant/neoadjuvant therapy, and mutation status. Two patients (16%) had grade 3–4 treatment-related adverse events. Conclusions: Nivolumab plus ipilimumab demonstrated significant clinical benefit and was well tolerated in patients with MSI-H mCRC. Clinical evaluation of ICIs in first-line metastatic, adjuvant and neoadjuvant settings and in combination with other therapies are ongoing.
Photosensitive pro-drug nanoassemblies harboring a chemotherapeutic dormancy function potentiates cancer immunotherapy
Authors: Jianjun Cheng, Haitian Zhao, Bin Li, Hua Zhang, Qianyu Zhao, Shiyao Fu, Ying Han, Weihong Lu, Jiahua Shi, Xin Yang
Journal: Acta Pharmaceutica Sinica B (2022)

Immunotherapy combined with effective therapeutics such as chemotherapy and photodynamic therapy have been shown to be a successful strategy to activate anti-tumor immune responses for improved anticancer treatment. However, developing multifunctional biodegradable, biocompatible, low-toxic but highly efficient, and clinically available transformed nano-immunostimulants remains a challenge and is in great demand. Herein, we report and design of a novel carrier-free photo-chemotherapeutic nano-prodrug COS-BA/Ce6 NPs by combining three multifunctional components—a self-assembled natural small molecule betulinic acid (BA), a water-soluble chitosan oligosaccharide (COS), and a low toxic photosensitizer chlorin e6 (Ce6)—to augment the antitumor efficacy of the immune adjuvant anti-PD-L1-mediated cancer immunotherapy. We show that the designed nanodrugs harbored a smart and distinctive "dormancy" characteristic in chemotherapeutic effect with desired lower cytotoxicity, and multiple favorable therapeutic features including improved 1O2 generation induced by the reduced energy gap of Ce6, pH-responsiveness, good biodegradability, and biocompatibility, ensuring a highly efficient, synergistic photochemotherapy. Moreover, when combined with anti-PD-L1 therapy, both nano-coassembly based chemotherapy and chemotherapy/photodynamic therapy (PDT) could effectively activate antitumor immunity when treating primary or distant tumors, opening up potentially attractive possibilities for clinical immunotherapy.
Monitoring PD-L1 expression on circulating stromal cells in blood predicts PFS and OS in patients with metastatic NSCLC treated with PD-L1/PD-1 immunotherapy.
Authors: Jillian Moran, Daniel L Adams, Pablo Lopez Bravo, Jianzhong He, Yawei Qiao, Ting Xu, Zhongxing X. Liao, Kirby P Gardner, Cha-Mei Tang, Steven H. Lin
Journal: Journal of Clinical Oncology (2022)

8535 Background: Cancer Associated Macrophage Like cells (CAMLs), a circulating stromal cell found in cancer patients (pts) blood, are phagocytic giant macrophages that appear to parallel the inflammatory PD-L1 state of the tumor microenvironment. Previously, we demonstrated in local non-small cell lung carcinoma (NSCLC), CAML PD-L1 expression is dynamic and predicts response to PD-L1/PD-1 immunotherapies (IMTs) following sequential sampling before and after chemotherapy (chemo) induction (̃30days) based on progression free (PFS) &amp; overall survival (OS). However this has not been tested in metastatic NSCLC (mNSCLC). Here,we report the results of monitoring PD-L1 expression in CAMLs before and after chemo induction (̃30 days) to evaluate its predictive value in mNSCLC pts treated with or without IMT. Methods: A single blind multi-year prospective study was undertaken to test the relationship of PD-L1 expression in CAMLs to PFS &amp; OS, pre &amp; post chemo induction, in recurrent mNSCLC with (n = 41) or without (n = 41) additional anti-PD-L1/PD-1 IMTs. This included three IMTs: atezolizumab (n = 4), nivolumab (n = 8) or pembrolizumab (n = 29). We recruited 82 pts with pathologically confirmed recurrent mNSCLC prior to treatment for newly recurrent metastatic disease. Blood samples (15 mL) were taken at Baseline (BL), prior to chemo, and ̃30 days after chemotherapy (T1). Blood was filtered by CellSieve filtration &amp; CAMLs’ expression scored as a binary high/low, to evaluate PFS &amp; OS hazard ratios (HRs) by censored univariate &amp; multivariate analysis at 18 months. Results: CAMLs were found in 97% of all tested samples, 94% at BL &amp; 100% at T1. CAML PD-L1 at BL was found not to be associated with PFS or OS in pts treated with chemo alone (PFS p = 0.620 &amp; OS p = 0.673) or chemo+IMT (PFS p = 0.353 &amp; OS = 0.477) at 18 months. At T1, high CAML PD-L1 in pts treated with chemo alone had no significantly different PFS (HR = 1.3, p = 0.694) or OS (HR = 1.6 p = 0.503). However, high CAML PD-L1 at T1 in pts treated with chemo+IMT had significantly better PFS (HR = 3.1, 95%CI = 1.3-7.3, p = 0.019), and OS (HR = 3.4, 95%CI = 1.4-8.3, p = 0.014). Further subtyping &amp; analysis is ongoing to evaluate PFS and OS at 24 months. Conclusions: Our data suggests that in mNSCLC, PD-L1 expression in circulating CAMLs dynamically upregulates after induction with chemotherapy and appears to predict patients with increased benefit to PD-L1/PD-1 IMTs, though additional studies are needed to validate these findings.
Epidemiology of asymptomatic bacteriuria prior urological surgery: preliminary results of the retrospective and multicenter TOCUS study
Authors: K. Stessy, H. Robin, P. Bigot, M. Baboudjian, M. Françot, S. De Vergie, J. Rigaud, M. Chapuis, L. Brureau, C. Jousseaume, O. Karray, F. Kosseifi, S. Borojeni, E. Lechevallier, S. Bernardeau, F. Bruyère, B. Gondran-Tellier, M. Vallée
Journal: European Urology (2022)